Diisopropylethylamine → N-(1,3-dimethyl-5-isoquinolinyl)-N'-[3-fluoro-4-(trifluoromethyl)benzyl]urea

HRID 586010Notes

Reaction equation

HRID 586010 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH2:8][N:9]=[C:10]=[O:11])[CH:5]=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13].[CH3:16][C:17]1[C:26]2[CH:25]=[CH:24][CH:23]=[C:22]([NH2:27])[C:21]=2[CH:20]=[C:19]([CH3:28])[N:18]=1.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1>[CH3:16][C:17]1[C:26]2[C:21](=[C:22]([NH:27][C:10]([NH:9][CH2:8][C:6]3[CH:5]=[CH:4][C:3]([C:12]([F:13])([F:14])[F:15])=[C:2]([F:1])[CH:7]=3)=[O:11])[CH:23]=[CH:24][CH:25]=2)[CH:20]=[C:19]([CH3:28])[N:18]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 223375622-Fluoro-4-(isocyanatomethyl)-1-(trifluoromethyl)benzeneHCID 223376241,3-Dimethylisoquinolin-5-amine

Product 1

HCID 22032669N-(1,3-dimethyl-5-isoquinolinyl)-N'-[3-fluoro-4-(trifluoromethyl)benzyl]urea

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

The product from Example 205A (4.4 mmol) in toluene (10 mL) was treated with 1,3-dimethyl-5-isoquinolinamine (375 mg, 2.18 mmol) and DIEA (3.5 mL). The mixture was heated at 80° overnight. After cooling to room temperature, the precipitated solids were collected by filtration and chromatographed on silica gel (98:2 CH2Cl2:CH3OH to 95:5 CH2Cl2:CH3OH) to provide the title compound. The corresponding hydrochloride salt was prepared by treatment with methanolic HCl. 1H NMR (300 MHz, DMSO-d6) δ 8.72 (s, 1H), 8.13 (d, 1H, J=7.8 Hz), 7.75-7.83 (m, 2H), 7.61 (s, 1H), 7.38-7.51 (m, 3H), 7.18 (t, 1H, J=6.1 Hz), 4.46 (d, 2H, J=5.8 Hz), 2.84 (s, 3H), 2.59 (s, 3H); MS (ESI+) m/z 392 (M+H).

Workup

  1. temperatureThe mixture was heated at 80° overnight
  2. filtrationthe precipitated solids were collected by filtration
  3. customchromatographed on silica gel (98:2 CH2Cl2:CH3OH to 95:5 CH2Cl2:CH3OH)

Sources & evidence

ORD record
ord-d4b7bf2b00694cc98aa17dac449d9ee8
Source dataset
uspto-grants-2005_08
Patent number
US06933311B2

Reaction notes

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